Role of MCP-1 and MIP-1α in retinal neovascularization during postischemic inflammation in a mouse model of retinal neovascularization

• Published in: Journal of leukocyte biology Vol. 73; no. 1; pp. 137 - 144
• Main Authors: Yoshida, Shigeo, Yoshida, Ayako, Ishibashi, Tatsuro, Elner, Susan G., Elner, Victor M.
• Format: Journal Article
• Language: English
• Published: Society for Leukocyte Biology 01.01.2003
• Subjects: angiogenesis; cytokines; macrophages; retinal ischemia
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0302117

Macrophages are important participants in neovascularization. This study was designed to examine the role of the monocyte/macrophage chemotactic proteins, monocyte chemotactic protein‐1 (MCP‐1), and macrophage inflammatory protein‐1α (MIP‐1α) in a mouse model of oxygen‐induced ischemic retinopathy and to determine whether the morphology and distribution of macrophages/microglia are concomitantly altered. The MCP‐1, MIP‐1α mRNA levels increased at 3 h after ischemia. MCP‐1, MIP‐1α, and vascular endothelial growth factor protein levels were also increased markedly and were maximal on days 1,0.5, and 1, respectively, after ischemia. In situ hybridization showed that MCP‐1 and MIP‐1α were localized in the hypoxic inner retina. Immunostaining demonstrated that the macrophages/microglia in the retina had morphological changes with enlarged processes, and some were closely associated with neovascular tufts at postnatal day 17. Coadministration of the neutralizing antibodies against MCP‐1 and MIP‐1α inhibited retinal neovascularization by 30%. Our data suggest that MCP‐1 and MIP‐1α are involved in the induction of retinal neovascularization and play a role in the inflammation induced by the ischemic retinopathy, possibly by modulating or attracting macrophages/microglia.